New Advances in Traumatic Brain Injury

Sara Cohen, MD


January 25, 2017

In the United States, there are 1.7 million yearly emergency department visits, hospitalizations, and deaths related to traumatic brain injury (TBI).[1] This shockingly large number is likely an underestimate of the true number of brain injuries; roughly 30%-45% of people who suffer concussions, especially athletes under pressure to perform, never present to a healthcare provider.[2]

Furthermore, in the setting of the recent Middle East conflicts, brain injury in the military has reached epidemic proportions, with the RAND Corporation reporting a 19% incidence of in-theater concussion.[3] With such a large number of people affected, considerable research efforts are now being dedicated to the diagnosis and treatment of mild to severe TBI.

Most TBIs (85%-90%) are mild in severity. The precise definition of mild TBI varies depending on the source but is generally described as an acute brain injury resulting from mechanical energy to the head from external forces with loss of consciousness less than 30 minutes, posttraumatic amnesia less than 24 hours, and Glasgow Coma Scale (GCS) score of 13-15 after 30 minutes post-injury or on presentation for healthcare.[4] The term "concussion" is often used interchangeably with mild TBI.

New research in brain injury has focused on the best method to evaluate patients with concussion. For example, when should a head CT be obtained in a patient presenting to the emergency department? In a patient with a GCS score of 15, only 5% will have findings of hemorrhage on head CT; and while this percentage rises to 30% in patients with a GCS score of 13, only 1% of all patients with mild TBI (GCS score of 13-15) will have findings on head CT that require neurosurgical intervention.[5]

Moreover, head CT has a very low specificity for diffuse axonal injury that may result in significant symptoms and poorer prognosis, and it also confers exposure to radiation. Brain MRI is a much more sensitive test for diffuse injuries, but utilization is limited by cost and availability at certain institutions.

For this reason, there's been interest in serum biomarkers as tools in diagnosing and prognosticating mild TBI. Biomarkers that have been recently studied include neuron-specific enolase, creatine kinase isoenzyme, myelin basic protein, glial fibrillary acidic protein, fatty acid-binding proteins, cleaved tau, ubiquitin C-terminal hydrolase-L1, and alpha II-spectrin breakdown products. However, the most widely studied biomarker is S100β.

Biomarker S100β is the major calcium-binding protein in astrocytes and is a marker of astrocyte injury or death. Because S100β is released after a brain injury, serum S100β levels could theoretically serve as a marker of injury. There have been several studies that have correlated serum S100β level with abnormalities on head CT, indicating that use of this biomarker could reduce the number of head CTs performed by 30%. MRI abnormalities have also been correlated with elevated serum S100β levels. In addition, S100β may be helpful in predicting which patients will suffer from prolonged postconcussive symptoms—such as headache, sleep disturbances, and mood changes—following mild TBI.[6] However, despite much promising research, at this time, none of the biomarkers being studied has been validated for use in TBI.

Magnetic resonance (MR) spectroscopy is a functional assessment of the brain's metabolism and has been emerging as a valid tool in assessing metabolic changes following mild TBI. N-acetylaspartate (NAA) is the most abundant neuronal-specific N-acetylated amino acid in cerebral tissue and has been hypothesized to be useful in measuring damage to the brain following concussion. Measurement of NAA by MR spectroscopy is emerging as a possible mechanism to monitor recovery after concussion, predict favorable outcomes, and determine when it is safe for an athlete to return to play.[7]


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